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Biomedical subjects

S Cooper

Publications and source records attributed to S Cooper.

At least 343 records · Page 19Linked to original sources
PubMed1978

In irradiation chimeras, K or D regions of the chimeric host, not of the donor lymphocytes, determine immune responsiveness of antiviral cytotoxic T cells.

The H-2 haplotype of the chimeric host determines the responder phenotype of maturing T cells. Spleen cells of chimeric mice formed when (K(k) nonresponder to D(b) x K(b) responder to D(b) plus vaccinia)F(1) bone marrow cells were used to reconstitute K(b)D(b) (C57BL/6 D(b) responder) irradiated recipients generated high levels of D(b) plus vaccinia virus-specific cytotoxic T cells. The same stem cells used to reconstitute K(k)D(b) (B10.A (2R) D(b) nonresponder) irradiated recipients resulted in spleen cells that responded well to K plus vaccinia, but responsiveness to D(b) was low. A generally low response to D(k) plus vaccinia, which seems to be regulated by D(k), was confirmed in chimeras. Thus, K(d)D(d) (D(d) plus vaccinia responder) stem cells differentiating in a K(d)D(k) chimeric host failed to generate a measurable response to D(k) plus vaccinia. In contrast, stem cells from K(d)D(k) (D(k) plus vaccinia low responders) differentiating in a K(d)D(d) (K(d) and D(d) high responders to vaccinia) host do generate responsiveness to D(d) plus vaccinia. These results indicate that in chimeras, the Ir phenotype is independent of the donor T cell's Ir genotype, and that thymic selection of a T cell's restriction specificity for a particular H-2 allele of the chimeric host also defines that T cell's/r phenotype.

Animals↗
PubMed1978

Ir-genes in H-2 regulate generation of anti-viral cytotoxic T cells. Mapping to K or D and dominance of unresponsiveness.

H-2 dependent and virus-specific Ir genes regulate the generation of primary virus-specific K or D restricted cytotoxic T-cell responses in vivo. The following examples have been analyzed in some detail: first, Dk restricted responses to vaccinia in Sendai viruses are at least 30 times lower than the corresponding K-restricted responses irrespective of the H-2 haplotypes (k, b, d, dxs, dxq) of K and I regions; in contrast, LCMV infection generates high responses to Dk. These findings are consistent with but do not prove that this Ir gene maps to D. Second, Db restricted responses to vaccinia and Sendai viruses are high in strains possessing the Kq or KbIb, KbaIb haplotype, are very low in strains with Kk, and relatively low in mouse strains of the KdI-Ad haplotype; LCMV generates high Db restricted response in the presence of Kk. This Ir gene for the response to vaccinia and Sendai viruses maps to K since B10.BYR (KqIkdDb) is a responder and B10.A (2R) is a nonresponder (KkIkdDb). Third, virus and K or D allele specific nonresponsiveness is dominant with variable penetrance; in heterozygous mice the nonresponder Kk allele over-rides responsiveness normally found in KbDb or KqDb combinations. Fourth, when (responder X nonresponder)F1 lymphocytes are stimulated in an environment expressing vaccinia virus plus only a high responder Kb or Kq allelle and Db, response to vaccinia Db is high; in contrast when the same F1 cells are stimulated in an environment expressing the low responder allele Kk, response to vaccinia Db is low. Thus absence of Kk during immunization allows generation of high responsive Db restricted vaccinia specific cytotoxic T cells. The Dk dependent low response to vaccinia Dk can be explained by a preclusion rule or by failure of vaccinia to complex with Db; however the analysis of Kk dependent low response to vaccinia Db does not support these explanations or that self-tolerance is responsible for this Ir effect but is compatible with the interpretation that Kk vaccinia is immunodominant over Db vaccinia. These results are discussed with respect to (a) possible mechanisms of regulation by Ir genes and (b) H-2 polymorphism and HLA-disease association.

Alleles↗
PubMed1978

On the thymus in the differentiation of "H-2 self-recognition" by T cells: evidence for dual recognition?

In the thymus, precursor T cells differentiate recognition structures for self that are specific for the H-2K, D, and I markers expressed by the thymic epithelium. Thus recognition of self-H-2 differentiates independently of the T cells H-2 type and independently of recognition of nonself antigen X. This is readily compatible with dual recognition by T cells but does not formally exclude a single recognition model. These conclusions derive from experiments with bone marrow and thymic chimeras. Irradiated mice reconstituted with bone marrow to form chimeras of (A X B)F1 leads to A type generate virus-specific cytotoxic T cells for infected targets A only. Therefore, the H-2 type of the host determines the H-2-restricted activity of killer T cells alone. In contrast, chimeras made by reconstituting irradiated A mice with adult spleen cells of (A X B)F1 origin generate virus-specific cytotoxic activity for infected A and B targets, suggesting that mature T cells do not change their self-specificity readily. (A X B)F1 leads to (A X C)F1 and (KAIA/DC) leads to (KAIA/DB) irradiation bone marrow chimeras responded against infected A but not B or C targets. This suggests that cytotoxicity is not generated against DC because it is abscent from the host's thymus epithelium and not against DB because it is not expressed by the reconstituting lymphoreticular system. (KBIB/DA) leads to (KCIC/DA) K, I incompatible, or completely H-2 incompatible A leads to B chimeras fail to generate any measurable virus specific cytotoxicity, indicating the necessity for I-specific helper T cells for the generation of killer T cells. Finally adult thymectomized, irradiated and bone marrow reconstituted (A X B)F1 mice, transplanted with an irradiated thymus of A origin, generate virus-specific cytotoxic T cells specific for infected A targets but not for B targets; this result formally demonstrates the crucial role of thymic epithelial cells in the differentiation of anti-self-H-2 specificities of T cells.

Animals↗
PubMed1978

The lymphoreticular system in triggering virus plus self-specific cytotoxic T cells: evidence for T help.

The thymus determines the spectrum of the receptor specificities of differentiating T cells for self-H-2; however, the phenotypic expression of T cell's specificity for self plus virus is determined predominantly by the H-2 type of the antigen presenting cells of the peripheral lymphoreticular system. Furthermore, virus specific helper T cells are essential for the generation of virus-specific cytotoxic T cells. For cooperation between mature T cells and other lymphocytes to be functional in chimeras, thymic epithelial cells and lymphohemopoietic stem cells must share the I region; killer T-cell generation also requires in addition compatibility for at least one K or D region. These conclusions derive from the following experiments: A leads to (A X B)F1 chimeric lymphocytes do produce virus-specific cytotoxic T-cell activity for infected A but not for infected B cells; when sensitized in an acutely irradiated and infected recipient (A X B)F1 these chimeric lymphocytes respond to both infected A and B. Therefore the predominantly immunogenically infected cells of chimeras the radiosensitive and by donor stem cells replaced lymphoreticular cells. In this adoptive priming model (KAIA/DB leads to KAIA/DC) chimeric lymphocytes could be sensitized in irradiated and infected F1 against KA and DC but not against infected DB targets. In contrast KBIB/DA leads to KCIC/DA chimeras' lymphocytes could not be sensitized at all in appropriately irradiated and infected F1 recipients. Thus these latter chimeras probably lack functional I-specific T helper cells that are essential for the generation of T killer cells against infected D compatible targets. If T cells learn in the thymus to recognize H-21 or K, D markers that are not at least partially carried themselves in other cells of the lymphoreticular system immunological interactions will be impossible and this paradox situation results in phenotypic immune incompetence in vivo.

Animals↗
PubMed1978

Probabilistic behavior of DNA segregation in Escherichia coli.

The pattern of segregation of DNA in Escherichia coli B/rK was analyzed by using the Methocel technique for forming chains of cells and the membrane binding elution method. Strain B/rK was shown to have a relatively high degree of nonrandom segregation and was used in a critical experiment to test the proposal that only one DNA strand acts nonrandomly during segregation. Thymidine-labeled cells were bound to a nitrocellulose membrane, and newly dividing cells were eluted from the membrane for six generations. The segregation of DNA in the eluted cells as well as in the cells bound to the membrane was examined by the Methocel technique. No difference in segregation was found between the two populations of cells, a result which indicates that the two strands are equivalent in segregation and that the pattern of segregation is not the result of a permanent binding of any strand to a pole of a cell.

Cell Division↗
PubMed1978

Evaluation of oxidative phosphorylation in hearts from euthyroid, hypothyroid, and hyperthyroid rats.

The energy relationships between cytosolic and mitochondrial metabolism were studied in the hearts from euthyroid, hypothyroid, and hyperthyroid rats. Isolated mitochondria showed high respiratory control ratios and impermeability to exogenous NADH. Hypo- and hyperthyroidism, respectively, resulted in lower and higher contents of both cytochromes per mitochondrion and mitochondrial protein per gram of wet weight of heart without changes in the ratio of cytochrome c to cytochrome aa3. In isolated perfused heart, the hyperthyroid state led to an increase in work rate and thereby an elevation of Vo2, which resulted in an increase oxidation-reduction turnover number for the cytochromes. An agreement was found between [ATP]/[ADP][Pi] of cytosolic free adenine nucleotides and the value calculated from a mathematical model of mitochondrial respiration. This implies that mitochondrial respiration is controlled at the cytochrome oxidase reaction and that oxidative phosphorylation in intact tissue is tightly coupled irrespective of thyroid state. It is concluded that thyroid hormone causes an increase in the mitochondrial mass, mitochondrial cytochrome content, and respiratory rate, and consequently expands the capacity of oxidative metabolism without an uncoupling effect on oxidative phosphorylation.

Adenine Nucleotides↗
PubMed1977

Immunodepression, ascites tumour and lactate dehydrogenase virus.

The delayed hypersensitivity (DH) response to picryl chloride was studied in Ehrlich ascites tumour-bearing and normal control mice. A significant depression of the DH response was found in the tumour-bearing mice, which was associated with a marked elevation of serum lactate dehydrogenase (LDH). Depression of DH was also observed in mice receiving cell-free ascitic fluid. These mice also showed an elevated serum LDH which is assumed to be associated with the lactate dehydrogenase virus. A method for assaying DH in vivo is described.

Animals↗
PubMed1977

Light-driven sodium transport in sub-bacterial particles of Halobacterium halobium.

Light-induced Na+ efflux was observed in sub-bacterial particles of Halobacterium halobium loaded and suspended in 4 M NaCl solution. The Na+ efflux was not ATP driven, since ATPase inhibitors were without effect or even enhanced efflux at low light intensity. Uncouplers, on the other hand, inhibited Na+ efflux, the inhibition being complete at low light intensity. The Na+ efflux was accompanied by proton influx. Both processes were dependent on light intensity, unaffected or enhanced by ATPase inhibitors and similarly affected by uncouplers. Proton influx was not observed in particles loaded with 4 M KCl instead of 4 M NaCl. Na+ transport in the dark could be induced by artificial formation of a pH difference across the membrane; changing the sign of the pH difference reversed the direction of the Na+ transport. Proton influx in the dark followed the artificial formation of a sodium gradient [Na+]in less than [Na+]out). These results may be explained by a Na+/H+ antiport mechanism. The fluxes of Na+ and H+ were of comparable magnitude, but the initial rate of Cl- efflux in the same experiment was one-third of the initial rate of Na+ efflux. Consequently Cl- is not regarded as a participant in the Na+ efflux mechanism.

Arsenates↗
PubMed1977

Observed and predicted accumulation of local anaesthetic agents during continuous extradural analgesia.

After lumbar extradural injections of ligocaine or etidocaine for surgical anaesthesia further accumulation in the plasma was minimal following top-up injections for pain relief after operation. The dose regimens were: 20 ml of 2% plain lignocaine HCl solution for surgical anaesthesia followed by 10 ml every 1 h until 4 h, and 20 ml of 1% plain etidocaine HCl solution for surgical anaesthesia followed by 10 ml every 2 h until 8 h. Plasma drug concentrations measured after initial doses were used to predict those following successive doses. Agreement between predicted and experimental values was good and further projections were made concerning the local accumulation of etidocaine.

Acetanilides↗
PubMed1977

Plasma concentrations of local anaesthetics after interscalene brachial plexus block.

Plasma concentrations of local anaesthetic agents have been measured after 40 interscalene brachial plexus blocks in 39 patients, using lignocaine, prilocaine, bupivacaine and etidocaine. Lignocaine produced greater concentrations than prilocaine, and bupivacaine greater concentrations than etidocaine. The addition of adrenaline resulted in much lower concentrations in the case of all four agents.

Anesthetics, Local↗
PubMed1977

Medium-dependent variation of deoxyribonucleic acid segregation in Escherichia coli.

The degree to which deoxyribonucleic acid segregates nonrandomly has been investigated for Escherichia coli B/r growing in different media. The degree of nonrandom segregation observed is dependent on the medium, with segregation becoming less random as the growth rate decreases. This indicates that there must be some varying probabilistic component to the segregation process. A probabilistic modification of the Pierucci-Zuchowski model is proposed as well as a probabilistic model, in which it is proposed that deoxyribonucleic acid strands segregate, with a probability greater than 0.5, in the same direction (toward the same pole) as at the previous cell division.

Cell Division↗
PubMed1976

Contrasts in HMO and fee-for-service performance.

This study compares various aspects of HMO performance in 10 plans with that of the fee-for-service system for the Medicaid population. Additionally, it examines utilization differences between several types of HMO's, grouped according to organization and provider payment. Four areas of behavior were studied--enrollment selectivity, utilization of services, accessibility of care, and satisfaction. The only significant difference between the two systems was in hospital utilization. Group-practice MNO's had significantly lower hospital utilization than the fee-for-service groups: foundation HMO's did not. This difference seems to indicate that capitation payment to an HMO alone is not significant enough to produce major changes in utilization and that the organized multispecialty group-practice arrangement with largely salaried physicians may be more significant. For the other variables--previous health status, ambulatory-care use (including preventive care), accessibility, and satisfaction--the two groups were remarkably similar.

Adolescent↗
PubMed1975

Physical properties of some ribosomal proteins in solution and evidence for molecular interactions between isolated ribosomal proteins.

Many previous studies have been directed toward obtaining a physical visualization of the relationship between the protein and RNA in the ribosomal subunits isolated from Escherichia coli. The current study is the first report where an attempt has been made to directly assess interactions between a pair of isolated ribosomal proteins separate from the intact system by means of sedimentation equilibrium analysis. The molecular weights of the proteins S3, S4, S5, S6, S7, S8, and S20 from the 30S subunit of the E. coli ribosome were determined under conditions of assembly of the subunit by sedimentation equilibrium. All of the proteins exhibited molecular weights consistent with monomeric behavior (i.e., in agreement with the measurement of the ultimate molecular weight in denaturing solvents as reported in other studies as well as in the current study) except S8 which indicates a tendency to self-associate. Hydrodynamic measurements on the proteins indicate that these proteins are not completely disorganized in solution such as a random coil, although not as compact as globular proteins. The frictional coefficient ratios found for these ribosomal proteins range from 1.4 to 1.9. The hydrodynamic data are discussed as containing some evidence that stable interaction sites could exist in the proteins. The molecular weight data are considered pertinent to a sedimentation equilibrium study of protein-protein interactions that may be occurring in the ribosomal subunits. Two proteins, S3 and S5, considered in this investigation were found to exhibit no tendency to self-associate under conditions of reassembly. When the two proteins are mixed under those same conditions, however, a species with a molecular weight greater than that of either S3 or S5 is observed to be formed. The interpretation is presented that a molecular interaction between S3 and S5 is the cause. The system is described as containing S3, S5, and a complex between S3 and S5 with a stoichiometry of 1:1 and an association equilibrium constant of 5.7 times 10-5 l./mol (delta G-o equals minus 7.25 kcal/mol). Since the association appears to be specific and of moderate strength, it is concluded that the interaction could have some pertinence with respect to conferring a structural arrangement in the ribosomal subunit. Moreover, it is concluded that protein-protein interactions, in general, must be considered in addition to the well documented significant RNA-protein relationships when models for ribosome structure and assembly are formulated.

Amino Acids↗